Methoctramine, a selective M2 muscarinic cholinergic receptor antagonist, has been reported to activate phosphoinositide breakdown at high concentrations. Its polyamine structure suggests a putative activation of guanine nucleotide-binding proteins (G proteins). Incubation of methoctramine with rat peritoneal mast cells resulted in a dose-dependent noncytotoxic histamine release, with an EC50 of 20 microM and a maximum effect at 1 mM. Atropine, pirenzepine and HHSiD neither inhibited methoctramine-induced histamine release nor stimulated histamine release. Histamine release and inositol phosphates generation induced by methoctramine were both inhibited by pertussis toxin pretreatment. Benzalkonium chloride, a selective inhibitor of histamine secretion induced by basic secretagogues, inhibited the secretory response to methoctramine. [p-Glu5, D-Trp7,9,l0]-SPs5-11 (GPAnt-2), a well-characterized antagonist of G proteins, blocked the methoctramine-induced histamine release when the antagonist was allowed to reach its intracellular target by streptolysin O-permeabilization. The response to methoctramine was prevented by the hydrolysis of sialic acid residues of the cell surface by neuraminidase. The response of mast cells was restored by permeabilization of the plasma membrane. These results demonstrate that methoctramine, following its entry into the cell and the involvement of pertussis toxin-sensitive G proteins, activates phosphoinositide hydrolysis leading to mast cell exocytosis. [less ▲]

Using conservation of energy—a fundamental property of closed classical and quantum mechanical systems— we develop an efficient gradient-domain machine learning (GDML) approach to construct accurate molecular force fields using a restricted number of samples from ab initio molecular dynamics (AIMD) trajectories. The GDML implementation is able to reproduce global potential energy surfaces of intermediate-sized molecules with an accuracy of 0.3 kcal mol−1 for energies and 1 kcal mol−1 Å−1 for atomic forces using only 1000 conformational geometries for training. We demonstrate this accuracy for AIMD trajectories of molecules, including benzene, toluene, naphthalene, ethanol, uracil, and aspirin. The challenge of constructing conservative force fields is accomplished in our work by learning in a Hilbert space of vector-valued functions that obey the law of energy conservation. The GDML approach enables quantitative molecular dynamics simulations for molecules at a fraction of cost of explicit AIMD calculations, thereby allowing the construction of efficient force fields with the accuracy and transferability of high-level ab initio methods. [less ▲]

The combination of modern scientific computing with electronic structure theory can lead to an unprecedented amount of data amenable to intelligent data analysis for the identification of meaningful ... [more ▼]

The combination of modern scientific computing with electronic structure theory can lead to an unprecedented amount of data amenable to intelligent data analysis for the identification of meaningful, novel and predictive structure-property relationships. Such relationships enable high-throughput screening for relevant properties in an exponentially growing pool of virtual compounds that are synthetically accessible. Here, we present a machine learning model, trained on a database of ab initio calculation results for thousands of organic molecules, that simultaneously predicts multiple electronic ground- and excited-state properties. The properties include atomization energy polarizability, frontier orbital eigenvalues, ionization potential electron affinity and excitation energies. The machine learning model is based on a deep multi-task artificial neural network, exploiting the underlying correlations between various molecular properties. The input is identical to ab initio methods, i.e. nuclear charges and Cartesian coordinates of all atoms. For small organic molecules, the accuracy of such a `quantum machine' is similar, and sometimes superior, to modern quantum-chemical methods-at negligible computational cost. [less ▲]

in IEEE Transactions on Network and Service Management (2010), 7(4), 244-257

Being able to fingerprint devices and services, i.e., remotely identify running code, is a powerful service for both security assessment and inventory management. This paper describes two novel ... [more ▼]

Being able to fingerprint devices and services, i.e., remotely identify running code, is a powerful service for both security assessment and inventory management. This paper describes two novel fingerprinting techniques supported by isomorphic based distances which are adapted for measuring the similarity between two syntactic trees. The first method leverages the support vector machines paradigm and requires a learning stage. The second method operates in an unsupervised manner thanks to a new classification algorithm derived from the ROCK and QROCK algorithms. It provides an efficient and accurate classification. We highlight the use of such classification techniques for identifying the remote running applications. The approaches are validated through extensive experimentations on SIP (Session Initiation Protocol) for evaluating the impact of the different parameters and identifying the best configuration before applying the techniques to network traces collected by a real operator. [less ▲]

Machine Learning-based malware detection is a promis- ing scalable method for identifying suspicious applica- tions. In particular, in today’s mobile computing realm where thousands of applications are daily poured into markets, such a technique could be valuable to guaran- tee a strong filtering of malicious apps. The success of machine-learning approaches however is highly de- pendent on (1) the quality of the datasets that are used for training and of (2) the appropriateness of the tested datasets with regards to the built classifiers. Unfortu- nately, there is scarce mention of these aspects in the evaluation of existing state-of-the-art approaches in the literature. In this paper, we consider the relevance of history in the construction of datasets, to highlight its impact on the performance of the malware detection scheme. Typ- ically, we show that simply picking a random set of known malware to train a malware detector, as it is done in most assessment scenarios from the literature, yields significantly biased results. In the process of assessing the extent of this impact through various experiments, we were also able to confirm a number of intuitive assump- tions about Android malware. For instance, we discuss the existence of Android malware lineages and how they could impact the performance of malware detection in the wild. [less ▲]